Syndromic ciliopathy: a taiwanese single-center study.

BACKGROUND: Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes. METHODS: The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment. RESULTS: A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation. CONCLUSIONS: Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.

Correlates of disordered eating and insulin restriction behavior and its association with psychological health in Taiwanese youths with diabetes mellitus.

BACKGROUND: Adolescents and young adults (AYAs) with diabetes mellitus (DM) are prone to eating disorders that may worsen metabolic control. This study investigated the clinical and behavioral correlates of disordered eating and insulin restriction (DE/IR) behavior and its association with psychological health among AYAs with DM. METHODS: We enrolled patients with DM aged 10-30 years receiving insulin treatment in a tertiary medical center from 2019 to 2021. After obtaining informed consent, we assessed various visit-to-visit HbA1c measures indicating glycemic control, DE/IR behavior using the modified SCOFF questionnaire, weight-control practices (e.g., self-medication, induced vomiting, and over-exercising), and anxious and depressive symptoms using the Hospital Anxiety and Depression Scale. Correlation and hierarchical regression analyses were applied to understand the clinical and behavioral correlates of DE/IR behavior and its association with anxiety and depression. RESULTS: Among the 110 patients with type 1 and type 2 DM recruited, we found 17.6% restricting insulin use and 6.3% self-medicating for weight control (higher in type 2 DM than type 1 DM). Hierarchical regression analyses showed HbA1c standard deviation (odds ratio = 2.18, [95% confidence interval 1.07-4.42]), body image (1.83, [1.05-3.20]), and dieting (4.74, [1.70-13.23]) associated with DE/IR behavior. Moreover, DE/IR behavior was further associated with anxiety (1.17 [1.08-1.27]) and depression (1.12 [1.03-1.22]). CONCLUSION: DE/IR behavior is not uncommon among AYAs with DM, particularly those with type 2 DM, and may be associated with anxiety and depressive symptoms. In addition, HbA1c variability is correlated with DE/IR behavior, and the clinical implications need further exploration.

Whole exome sequencing identifies a novel FRAS1 mutation and aids in vitro fertilization with preimplantation genetic diagnosis in Fraser syndrome.

OBJECTIVE: To demonstrate the picture of a woman who had three times of pregnancies but fetuses were complicated with Fraser syndrome, a rare genetic disorder with multiple congenital anomalies. CASE REPORT: Here are three complicated pregnancies with predominant features of severe oligohydramnios and other variable intrafamilial presentations. We made a definite diagnosis, Fraser syndrome, with the assistance of whole exome sequencing (WES) via umbilical blood of the second and third fetus. The provision of a preimplantation diagnosis helped contribute a healthy newborn in this family. CONCLUSION: This paper provides insights into obscure antenatal presentations of Fraser syndrome with intrafamilial variance. Clinical uncertainty at the fetal stage suggests the role of WES to reach a final diagnosis, and a preimplantation diagnosis is applicable to avoid recurrence of genetic disorders in subsequent pregnancies.